Posology : מינונים

4.2   Posology and method of administration


Posology
Epoprostenol is only indicated for continuous infusion by intravenous route.

Treatment should only be initiated and monitored by a physician experienced in the treatment of pulmonary arterial hypertension.

Short-term (acute) dose ranging:

This procedure should be conducted in a hospital with adequate resuscitation equipment.
A short-term dose-ranging procedure administered via either a peripheral or central venous line is required to determine the long-term infusion rate. The infusion rate is initiated at 2 nanograms/kg/min and increased by increments of 2 nanograms/kg/min every 15 min or longer until maximum haemodynamic benefit or dose- limiting pharmacological effects are elicited.
If the initial infusion rate of 2 nanograms/kg/min is not tolerated, a lower dose which is tolerated by the patient should be identified.

Long-term continuous infusion:

Long-term continuous infusion of Flolan should be administered through a central venous catheter.
Temporary peripheral i.v. infusions may be used until central access is established. Long-term infusions should be initiated at 4 nanograms/kg/min less than the maximum tolerated infusion rate determined during short-term dose-ranging. If the maximum tolerated infusion rate is 5 nanograms/kg/min or less, then the long-term infusion should be started at 1 nanograms/kg/min.

Dosage adjustments:

Changes in the long-term infusion rate should be based on persistence, recurrence or worsening of the patient ’s symptoms of pulmonary arterial hypertension or the occurrence of adverse reaction due to excessive doses of Flolan.

In general, the need for increases in dose from the initial long-term dose should be expected over time.
Increases in dose should be considered if symptoms of pulmonary arterial hypertension persist, or recur after improving. The infusion rate should be increased by 1 to 2 nanograms/kg/min increments at intervals sufficient to allow assessment of clinical response; these intervals should be of at least 15 min. Following establishment of a new infusion rate, the patient should be observed, and erect and supine blood pressure and heart rate monitored for several hours to ensure that the new dose is tolerated.

During long-term infusion, the occurrence of dose-related pharmacological events similar to those observed during the dose-ranging period may necessitate a decrease in infusion rate, but the adverse reactions may occasionally resolve without dosage adjustment. Dosage decreases should be made gradually in 2 nanograms/kg/min decrements every 15 min or longer until the dose-limiting effects resolve. Abrupt withdrawal of Flolan or sudden large reductions in infusion rates should be avoided due to the risk of potential fatal rebound effect (see section 4.4). Except in life-threatening situations (e.g. unconsciousness, collapse, etc) infusion rates of Flolan should be adjusted only under the direction of a physician.

Elderly
There is no specific information on the use of Flolan in patients over 65 years for pulmonary arterial hypertension. In general, dose selection for an elderly patient should be made carefully, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other medicine therapy.

Paediatric population
The safety and efficacy of epoprostenol in children younger than 18 years have not yet been established.

Method of administration
Precautions to be taken before handling or administering the medicinal product 
Freshly prepared solutions for infusion (either as a concentrated solution or a further diluted solution) can be administered immediately or stored for up to 8 days at 2°C to 8°C prior to administration. Following this preparation or storage, the solution for infusion should be used within 72 hours at up to 25°C, or 48 hours at up to 30ºC, or 24 hours at up to 35 ºC, or 12 hours at up to 40 ºC.

Epoprostenol solution prepared with solvent (pH 11.7-12.3), must not be used with any preparation or administration materials containing polyethylene terephthalate (PET) or polyethylene terephthalate glycol (PETG; see section 6.2 and 6.6).

The reconstituted solution should be examined prior to administration. Its use is forbidden in the presence of a discoloration or particles.

For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.

Epoprostenol must not be administered as a bolus injection.